tbuckley/cabot-search huggingface dataset:
AB1222 NEUTROPHIL TO LYMPHOCYTE RATIO (NLR) PREDICTS FRACTURE IN PATIENTS ON LONG-TERM GLUCOCORTICOID.
Authors: J. Chen, T. T. Cheng, S. F. Yu, H. Y. Kang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Long-term glucocorticoid (GC) exposure leads to systemic bone loss and fracture. In addition, GC is known to increase white blood cell (WBC) amount and change the distribution of differential count (DC). Neutrophil-to-Lymphocyte ratio (NLR) has been studied as an optimal marker of subclinical inflammation, predicting the prognosis of cardiovascular diseases, cancers and even covid-19 infection. For patients under long-term GC exposure, the hemogram change might be a potential parameter to predict prognosis. <h3>Objectives</h3> This pilot study aims to investigate if GC related WBC-DC change, including NLR, is associated with future fractures during 3 years follow-up. <h3>Methods</h3> This retrospective study is based on a registry, conducted in Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2014 till April 2021, aimed to monitor bone mineral density (BMD) changes and fractures in patients with autoimmune diseases. All recruited patients were followed at least 3 years and took X-ray images annually to capture new fragility fracture, including morphometric vertebral fractures. We screened participants who used GC continuously at least 3 months before the index day. We recorded the complete blood count (CBC) and WBC-DC values at least twice during the period of 3 months before and after the index day, and excluded patients who were febrile, under infection status, diagnosed as cancers or cardiovascular diseases at the index day. The NLR was calculated by the absolute neutrophil count divided by absolute lymphocyte count individually. <h3>Results</h3> A total of 346 participants were enrolled in current study, and 101 (29.2%) suffered from new fragility fracture in 3 years. Among patients with fracture and non-fracture, conventional fracture risk factors, such as age, BMD, and previous fracture remained significantly different, while the WBC revealed no difference (Table 1). Nevertheless, the absolute neutrophil and lymphocyte count were significantly higher and lower in the fracture group, respectively, and no difference in the monocyte, eosinophil, and basophil count. We compared different WBC ratio, and NLR is significantly higher in the fracture group, providing the odds ratio of 1.24 (95% confidence interval 1.07-1.44, p=0.005). Figure 1 showed that the observed fracture risk raised as the NLR values increased. <h3>Conclusion</h3> In patients under long-term GC, NLR might be a helpful marker to predict fracture, and higher NLR indicates higher fracture risks. <h3>Acknowledgements</h3> This work was supported by funding grant CMRPG8J0331 from the Chang Gung Memorial Hospital (https://www.cgmh.org.tw). <h3>Disclosure of Interests</h3> None Declared.
AB1225 ASSOCIATION BETWEEN BONE METABOLISM MARKERS AND INCREASES IN BONE MINERAL DENSITY IN PATIENTS WITH POSTMENOPAUSAL OSTEOPOROSIS TREATED WITH ROMOSOZUMAB
Authors: K. Hattori, Y. Kanayama
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoporosis is a metabolic bone disorder characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures [1]. Romosozumab (Rmab), a humanized monoclonal anti-sclerostin antibody, increases bone mineral density (BMD) and decreases fragility fractures in patients with postmenopausal osteoporosis (PMO) [2]. While an increase in type 1 amino-terminal propeptide (P1NP) and a decrease in tartrate-resistant acid phosphatase 5b (TRACP-5b) are observed early after administration of Rmab, the association between these changes in bone metabolic markers (BTMs) and increases in BMDs was still unknown. <h3>Objectives</h3> The aim of this research is to evaluate association between effect of Rmab on BMD and BTMs in patients with PMO. <h3>Methods</h3> Between March 2019 and August 2021, 34 patients with PMO, who were naïve to treatment of osteoporosis were included. The correlation between baseline characteristics, changes (%-) in BMDs in lumber (L-) and total hip (TH-) at 12 months (-M), and absolute values of P1NP and TRACP-5b and %P1NP and %TRACP-5b at 1, 3, 6M was calculated, respectively. Multiple regression analysis was performed on the factors that showed significant correlations to L- and TH-BMD, respectively. <h3>Results</h3> The mean age was 72.5 years old, mean BMI was 20.6 kg/m<sup>2</sup>, mean vertebral fractures were 2.1, mean L- and Th-BMD were 0.762 g/cm<sup>2</sup> and 0.589 g/cm<sup>2</sup>, and mean P1NP and TRACP-5b were 107.0 μg/L, and 640.3 mU/dL. %L- and %TH-BMD at 12M were 18.1% and 9.1%. %P1NP at 3M was positively correlated with %L-BMD at 12M, while %P1NP at 1 and 6M and TRACP-5b at each time point showed no significant correlation with %L-BMD at 12M. Multiple regression analysis confirmed that a great increase in P1NP at 3M was associated with a great increase in L-BMD at 12M. No correlation between either P1NP or TRACP-5b at each time point and %TH-BMD at 12M was observed. <h3>Conclusion</h3> We showed that a great increase in P1NP at 3M was a predictive factor of a great increase in L-BMD at 12M in patients with PMO treated with Rmab. On the other hand, there was no association between an increase in TH-BMD and BTMs including P1NP and TRACP-5b. <h3>References</h3> [1]Rachner TD, et al. Osteoporosis: now and the future. Lancet. 2011;9:1276-87. [2]McClung MR, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370:412-20. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1220 VERTEBRAL FRACTURE CHARACTERISTICS IN AN FLS UNIT ACCORDING TO THE IDENTIFICATION METHOD; EMERGENCY LIST, OUTPATIENT CLINIC OR VFA.
Authors: A. Naranjo, A. Molina, C. Rodriguez-Lozano, N. Martín, F. Santana, S. Fuentes, R. Navarro, T. Fernández-Varela, J. A. Lorenzo, A. Montesdeoca, S. Ojeda
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The risk o subsequent fracture is very high after a vertebral fracture (VF) <h3>Objectives</h3> To analyze the characteristics of patients with VF seen in a Fracture Liaison Service (FLS). <h3>Methods</h3> Our FLS cares for patients from the emergency list (URG), referred by hospital or primary care doctors (HPC) with VF &lt;12 months, and captured by DXA-VFA (Densitometry - VF Assessment) in patients with non-VF. The database included the FRAX items plus previous treatment and DXA results. Traumatic VFs or VFs with a known age &gt; 1 year, infiltrative or neoplastic diseases, and patients with contraindications for treatment were excluded. The number and grade of VF (Genant's scale) were analyzed. <h3>Results</h3> 570 patients have been included (Table 1). The most frequent route of identification was HPCfollowed by the emergency registry and detection by DXA-VFA. The patients identified by VFA did not report a previous VF, as did 25 of the HPC cases, referred by a report of fracture by the radiologistst or by detection in the consultation by the rheumatologist. Figure 1 shows the identification of patients over the years. We observed a higher percentage of grade 3 fractures in those identified in the emergency registry. Those identified by HPC had a higher average number of fractures and a higher percentage of osteoporosis by DXA. In this group there was a greater frequency of previous fracture, as well as rheumatoid arthritis and glucocorticoid use. Patients referred through HPC had a higher adherence to treatment compared with the other groups. The 69 patients detected by DXA-VFA consisted of 30 humerus fractures, 1 pelvic, and 38 forearm, mostly women with a single fracture and lower percentage of osteoporosis by DXA. The adherence to treatment has changed over the years. In 2021 and 2022 it was 93%, compared to 79% in 2012-2020. <h3>Conclusion</h3> All the ways to identify VF are important. The training campaign carried out in the healthcare area, including radiologists, has allowed us to improve the standard. The results will be helpful in the implementation and consolidation of the model based on FLS. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells
Authors: David P. Schrijver, Rutger J. Röring, Jeroen Deckers, Anne de Dreu, Yohana C. Toner, Geoffrey Prevot, Bram Priem, Jazz Munitz, Eveline G. Nugraha, Yuri van Elsas, Anthony Azzun, Tom Anbergen, Laszlo A. Groh, Anouk M. D. Becker, Carlos Pérez-Medina, Roderick S. Oosterwijk, Boris Novakovic, Simone J. C. F. M. Moorlag, Aron Jansen, Peter Pickkers, Matthijs Kox, Thijs J. Beldman, Ewelina Kluza, Mandy M. T. van Leent, Abraham J. P. Teunissen, Roy van der Meel, Zahi A. Fayad, Leo A. B. Joosten, Edward A. Fisher, Maarten Merkx, Mihai G. Netea, Willem J. M. Mulder
Journal: Nature Biomedical Engineering (2023)

Abstract Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
Authors: Alice Williamson, Dougall M. Norris, Xianyong Yin, K. Alaine Broadaway, Anne H. Moxley, Swarooparani Vadlamudi, Emma P. Wilson, Anne U. Jackson, Vasudha Ahuja, Mette K. Andersen, Zorayr Arzumanyan, Lori L. Bonnycastle, Stefan R. Bornstein, Maxi P. Bretschneider, Thomas A. Buchanan, Yi-Cheng Chang, Lee-Ming Chuang, Ren-Hua Chung, Tine D. Clausen, Peter Damm, Graciela E. Delgado, Vanessa D. de Mello, Josée Dupuis, Om P. Dwivedi, Michael R. Erdos, Lilian Fernandes Silva, Timothy M. Frayling, Christian Gieger, Mark O. Goodarzi, Xiuqing Guo, Stefan Gustafsson, Liisa Hakaste, Ulf Hammar, Gad Hatem, Sandra Herrmann, Kurt Højlund, Katrin Horn, Willa A. Hsueh, Yi-Jen Hung, Chii-Min Hwu, Anna Jonsson, Line L. Kårhus, Marcus E. Kleber, Peter Kovacs, Timo A. Lakka, Marie Lauzon, I-Te Lee, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Ching-Ti Liu, Jian’an Luan, Dina Mansour Aly, Elisabeth Mathiesen, Angela P. Moissl, Andrew P. Morris, Narisu Narisu, Nikolaos Perakakis, Annette Peters, Rashmi B. Prasad, Roman N. Rodionov, Kathryn Roll, Carsten F. Rundsten, Chloé Sarnowski, Kai Savonen, Markus Scholz, Sapna Sharma, Sara E. Stinson, Sufyan Suleman, Jingyi Tan, Kent D. Taylor, Matti Uusitupa, Dorte Vistisen, Daniel R. Witte, Romy Walther, Peitao Wu, Anny H. Xiang, Björn Zethelius, Vanessa D. de Mello, Emma Ahlqvist, Richard N. Bergman, Yii-Der Ida Chen, Francis S. Collins, Tove Fall, Jose C. Florez, Andreas Fritsche, Harald Grallert, Leif Groop, Torben Hansen, Heikki A. Koistinen, Pirjo Komulainen, Markku Laakso, Lars Lind, Markus Loeffler, Winfried März, James B. Meigs, Leslie J. Raffel, Rainer Rauramaa, Jerome I. Rotter, Peter E. H. Schwarz, Michael Stumvoll, Johan Sundström, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Robert Wagner, Inês Barroso, Mark Walker, Niels Grarup, Michael Boehnke, Nicholas J. Wareham, Karen L. Mohlke, Eleanor Wheeler, Stephen O’Rahilly, Daniel J. Fazakerley, Claudia Langenberg
Journal: Nature Genetics (2023)
Integrated multi-omics for rapid rare disease diagnosis on a national scale
Authors: Sebastian Lunke, Sophie E. Bouffler, Chirag V. Patel, Sarah A. Sandaradura, Meredith Wilson, Jason Pinner, Matthew F. Hunter, Christopher P. Barnett, Mathew Wallis, Benjamin Kamien, Tiong Y. Tan, Mary-Louise Freckmann, Belinda Chong, Dean Phelan, David Francis, Karin S. Kassahn, Thuong Ha, Song Gao, Peer Arts, Matilda R. Jackson, Hamish S. Scott, Stefanie Eggers, Simone Rowley, Kirsten Boggs, Ana Rakonjac, Gemma R. Brett, Michelle G. de Silva, Amanda Springer, Michelle Ward, Kirsty Stallard, Cas Simons, Thomas Conway, Andreas Halman, Nicole J. Van Bergen, Tim Sikora, Liana N. Semcesen, David A. Stroud, Alison G. Compton, David R. Thorburn, Katrina M. Bell, Simon Sadedin, Kathryn N. North, John Christodoulou, Zornitza Stark
Journal: Nature Medicine (2023)

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner.
Robust and data-efficient generalization of self-supervised machine learning for diagnostic imaging
Authors: Shekoofeh Azizi, Laura Culp, Jan Freyberg, Basil Mustafa, Sebastien Baur, Simon Kornblith, Ting Chen, Nenad Tomasev, Jovana Mitrović, Patricia Strachan, S. Sara Mahdavi, Ellery Wulczyn, Boris Babenko, Megan Walker, Aaron Loh, Po-Hsuan Cameron Chen, Yuan Liu, Pinal Bavishi, Scott Mayer McKinney, Jim Winkens, Abhijit Guha Roy, Zach Beaver, Fiona Ryan, Justin Krogue, Mozziyar Etemadi, Umesh Telang, Yun Liu, Lily Peng, Greg S. Corrado, Dale R. Webster, David Fleet, Geoffrey Hinton, Neil Houlsby, Alan Karthikesalingam, Mohammad Norouzi, Vivek Natarajan
Journal: Nature Biomedical Engineering (2023)
AB1233 IMPACT OF RHEUMATOID ARTHRITIS ON THE DENSITOMETRIC STATUS OF WOMEN
Authors: L. Rouached, J. Soua, S. Bouden, A. Ben Tekaya, I. Mahmoud, R. Tekaya, O. Saidane, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease. It can be associated with several comorbidities including osteoporosis (OP). The origin of this bone loss is multifactorial. A fracture episode is the complication of osteoporotic disease and constitutes all the gravity of this disease. <h3>Objectives</h3> The objective of this work was to evaluate bone densitometry (BMD) in women with RA and to identify its relationship with disease parameters. <h3>Methods</h3> This was a cross-sectional study, including patients followed for RA meeting the ACR/EULAR 2010 criteria. For each patient, disease parameters (duration of progression, activity score (DAS28 VS), functional impact (HAQ), corticosteroid intake) were assessed and BMD of the lumbar spine and femoral neck was performed in all patients. <h3>Results</h3> A total of 76 women were included, 66% of whom were postmenopausal. The mean age of the patients was 52.5±9.7 years and the mean duration of RA progression was 11.3±7.9 years. The mean DAS28 VS score was 4.3±1.4 and the mean HAQ was 0.98±0.8. Corticosteroid use was noted in 62 patients (81.5%) at a mean dose of 8.6±3.2mg/day. Regarding the densitometric profile of the patients, the mean BMD values at the vertebral and femoral sites were -1.4±1.3DS and 0.8±1.1DS respectively, and the prevalence of osteoporosis and osteopenia were 21.6% and 46.6% respectively. Patients with osteoporosis (OP) were older (p=0.00), and there was a significant relationship between OP and menopausal status (p=0.007). In contrast, disease parameters (function, activity, duration and treatment) were not associated with the occurrence of osteoporosis in our series: HAQ (p=0.6), disease duration (p=0.3), disease activity (p=0.3) or corticosteroid use (p=0.9). <h3>Conclusion</h3> OP is a frequent comorbidity associated with RA. It should be systematically detected because of its functional and vital complications. In our study, the occurrence of OP was more frequent at an older age during RA and menopausal status. There was no relation with the disease parameters. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Emerging Penetrating Neural Electrodes: In Pursuit of Large Scale and Longevity
Authors: Lan Luan, Rongkang Yin, Hanlin Zhu, Chong Xie
Journal: Annual Review of Biomedical Engineering (2023)

Penetrating neural electrodes provide a powerful approach to decipher brain circuitry by allowing for time-resolved electrical detections of individual action potentials. This unique capability has contributed tremendously to basic and translational neuroscience, enabling both fundamental understandings of brain functions and applications of human prosthetic devices that restore crucial sensations and movements. However, conventional approaches are limited by the scarce number of available sensing channels and compromised efficacy over long-term implantations. Recording longevity and scalability have become the most sought-after improvements in emerging technologies. In this review, we discuss the technological advances in the past 5–10 years that have enabled larger-scale, more detailed, and longer-lasting recordings of neural circuits at work than ever before. We present snapshots of the latest advances in penetration electrode technology, showcase their applications in animal models and humans, and outline the underlying design principles and considerations to fuel future technological development.
Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials
Authors: Margaret Haney, Monique Vallée, Sandy Fabre, Stephanie Collins Reed, Marion Zanese, Ghislaine Campistron, Caroline A. Arout, Richard W. Foltin, Ziva D. Cooper, Tonisha Kearney-Ramos, Mathilde Metna, Zuzana Justinova, Charles Schindler, Etienne Hebert-Chatelain, Luigi Bellocchio, Adeline Cathala, Andrea Bari, Roman Serrat, David B. Finlay, Filippo Caraci, Bastien Redon, Elena Martín-García, Arnau Busquets-Garcia, Isabelle Matias, Frances R. Levin, François-Xavier Felpin, Nicolas Simon, Daniela Cota, Umberto Spampinato, Rafael Maldonado, Yavin Shaham, Michelle Glass, Lars Lykke Thomsen, Helle Mengel, Giovanni Marsicano, Stéphanie Monlezun, Jean-Michel Revest, Pier Vincenzo Piazza
Journal: Nature Medicine (2023)

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis' positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.ClinicalTrials.gov identifiers: NCT03325595 , NCT03443895 and NCT03717272 .
Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease
Authors: Zhuoran Yin, Shawn Herron, Sebastian Silveira, Kilian Kleemann, Christian Gauthier, Dania Mallah, Yiran Cheng, Milica A. Margeta, Kristen M. Pitts, Jen-Li Barry, Ayshwarya Subramanian, Hannah Shorey, Wesley Brandao, Ana Durao, Jean-Christophe Delpech, Charlotte Madore, Mark Jedrychowski, Amrendra K. Ajay, Gopal Murugaiyan, Samuel W. Hersh, Seiko Ikezu, Tsuneya Ikezu, Oleg Butovsky
Journal: Nature Neuroscience (2023)
Engineering Therapeutics to Detoxify Hemoglobin, Heme, and Iron
Authors: Ivan S. Pires, François Berthiaume, Andre F. Palmer
Journal: Annual Review of Biomedical Engineering (2023)

Hemolysis (i.e., red blood cell lysis) can increase circulatory levels of cell-free hemoglobin (Hb) and its degradation by-products, namely heme (h) and iron (Fe). Under homeostasis, minor increases in these three hemolytic by-products (Hb/h/Fe) are rapidly scavenged and cleared by natural plasma proteins. Under certain pathophysiological conditions, scavenging systems become overwhelmed, leading to the accumulation of Hb/h/Fe in the circulation. Unfortunately, these species cause various side effects such as vasoconstriction, hypertension, and oxidative organ damage. Therefore, various therapeutics strategies are in development, ranging from supplementation with depleted plasma scavenger proteins to engineered biomimetic protein constructs capable of scavenging multiple hemolytic species. In this review, we briefly describe hemolysis and the characteristics of the major plasma-derived protein scavengers of Hb/h/Fe. Finally, we present novel engineering approaches designed to address the toxicity of these hemolytic by-products.
Collective action is needed to build a more just science system
Authors: Aisling Rayne, Hitaua Arahanga-Doyle, Bethany Cox, Murray P. Cox, Catherine M. Febria, Stephanie J. Galla, Shaun C. Hendy, Kirsten Locke, Anna Matheson, Aleksandra Pawlik, Tom Roa, Emma L. Sharp, Leilani A. Walker, Krushil Watene, Priscilla M. Wehi, Tammy E. Steeves
Journal: Nature Human Behaviour (2023)